ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1951T>C (p.Ser651Pro)

gnomAD frequency: 0.00001  dbSNP: rs754350357
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000793259 SCV000932605 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-12-18 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CLCN1 protein function. ClinVar contains an entry for this variant (Variation ID: 640272). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs754350357, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 651 of the CLCN1 protein (p.Ser651Pro). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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